(Pfizer) Mar 3, 2021 - The U.S. Food and Drug Administration (FDA) approved Pfizer Inc.’s supplemental New Drug Application (sNDA) for LORBRENA® (lorlatinib), expanding the indication to include first-line treatment of people with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC). LORBRENA is now indicated for adults with metastatic NSCLC whose tumors are ALK-positive as detected by an FDA-approved test. The FDA action also converts the 2018 accelerated approval to full approval. The application was approved under the FDA’s Real-Time Oncology Review (RTOR) pilot program.

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H. Jack West, MD (Posted: March 05, 2021)

Lorlatinib is an excellent ALK inhibitor, but beating crizotinib as first line therapy for patients with ALK-positive advanced NSCLC only puts it on par with alectinib as a current standard of care or other 2nd generation ALK inhibitors also superior to crizotinib and approved in this setting. Lorlatinib has good activity, both extracranial and intracranial, but its toxicity profile is somewhat idiosyncratic, particularly the neuro-behavioral issues. I do not think it emerges as offering a clear incremental benefit over alectinib. Moreover, using lorlatinib first line means that it isn't available as second line therapy, where it is arguably the leading option after progression on alectinib or another ALK inhibitor.

(FDA.gov) Feb 22, 2021 - On February 22, 2021, the Food and Drug Administration approved cemiplimab-rwlc (Libtayo, Regeneron Pharmaceuticals, Inc.) for the first-line treatment of patients with advanced non-small cell lung cancer (NSCLC) (locally advanced who are not candidates for surgical resection or definitive chemoradiation or metastatic) whose tumors have high PD-L1 expression (Tumor Proportion Score [TPS] > 50%) as determined by an FDA-approved test, with no EGFR, ALK or ROS1 aberrations. Efficacy was evaluated in Study 1624 (NCT03088540), a multi-center, randomized, open-label trial in 710 patients with locally advanced NSCLC who were not candidates for surgical resection or definitive chemoradiation or with metastatic NSCLC.

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H. Jack West, MD (Posted: February 23, 2021)

This approval now gives us a third option for the same clinical setting in which we already have pembrolizumab as a clear standard of care since it demonstrated significant superiority to chemotherapy alone in 2016. We also have atezolizumab that showed the same thing and currently serves as a rarely used understudy to pembrolizumab here, with no incremental benefit. Cemiplimab provides only further redundancy here. We should also reflect on the questionable ethics of running a trial that assigns half of the patients to a treatment that had been proven inferior to single agent immunotherapy from KEYNOTE-024 before the new trial started. Unfortunately, history has shown us that we should not expect the addition of more agents in the same setting to lead to improvements in pricing. I strongly suspect Regeneron will fail to price cemiplimab significantly lower than pembrolizumab or atezolizumab, which is the only factor that could differentiate it from better established competition in this market.

(MD Anderson) Feb 18, 2021 - The first randomized Phase II clinical trial to report on single and combined neoadjuvant immune checkpoint inhibitor therapy in stage I-III non-small cell lung cancer (NSCLC) found combination therapy produced a significant clinical benefit, as assessed by major pathologic response (MPR) rate, as well as enhanced tumor immune cell infiltration and immunological memory. Researchers from The University of Texas MD Anderson Cancer Center published the study results today in Nature Medicine.

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H. Jack West, MD (Posted: February 20, 2021)

Though there is a lot of focus on neoadjuvant immunotherapy for lung cancer, many if not most practicing oncologists will be seeking more established endpoints like a significant improvement in overall survival, or at least disease-free survival, rather than focusing on relatively newer variables like major pathological response that have been "retrofitted" as an endpoint of choice because they show a benefit quickly. Neoadjuvant immunotherapy or chemoimmunotherapy should generate great enthusiasm and become a new standard of care if and when it produces improvements in established endpoints in prospective, randomized phase 3 trials -- not before that. Immunologic endpoints don't counterbalance the side effects and costs of immunotherapy.